The proposed studies employ the fetal and newborn sheep as experimental models for the study of thyroid function during fetal life and in the newborn period. Kinetic studies of thyroxine (T4) and triiodothyronine (T3) metabolism in the fetus, placental hormone transfer, and placental transport of iodide will be conducted. The effect of fetal thyroidectomy on fetal growth and on T4 and T3 kinetics will be studied. The maturation of hypothalamic-pituitary-thyroid control in the fetus will be assessed by measuring the fetal putuitary response to thyrotropin releasing factor (TRF), and fetal thyroid response to thyrotropin, and the system response to T4 and T3 feedback and to intrauterine cooling. Studies of the chemical and binding characteristics of fetal thyroid hormone binding proteins are planned. Measurement of the thyroid hormone content of amniotic fluid and the kinetics of T4 and T3 turnover in amniotic fluid will be conducted as well as studies of fetal utilization of T4 and T3 injected into amniotic fluid. Finally the mechanism and significance of neonatal thyroid hyperactivity will be investigated in the newborn lamb.